The demand for homologous blood transfusions has reached an unprecedented level,driven by a declining donor population and the ever-increasing need for blood products.While significant advancements have been made in m...The demand for homologous blood transfusions has reached an unprecedented level,driven by a declining donor population and the ever-increasing need for blood products.While significant advancements have been made in medical equipment and techniques,a critical gap remains in developing an effective alternative to conventional blood transfusion.Medical research to find a proper blood substitute involves many previous experiments.The search for a blood substitute has been ongoing for patients for whom human blood is unavailable,with a few products showing promise in this field.Recent advancements in medical innovation have begun to address this challenge,notably through the development of artificial oxygen carriers(AOCs).These laboratory-synthesized alternatives to traditional blood transfusions offer a means of bypassing the need for human blood,particularly packed red blood cell(pRBC)transfusions.While AOCs fulfill the singular,critical role of in vivo oxygen delivery,the term is frequently used interchangeably with the broader concept of artificial blood.Various AOC products are currently in different stages of clinical development.Most Notable examples include Perftoran,which has been approved in Russia,Kazakhstan,Ukraine,the Kyrgyz Republic,and Mexico and has been administered to over 35,000 patients.Another significant product,Hemopure,has received clinical use approval in South Africa and Russia and has obtained expanded use approval from the United States Food and Drug Administration(USFDA).This article examines the landscape of AOCs,including their preparation methods,available products,regulatory approval status,current applications,limitations,and potential for future use in medical practice.This review article offers an overview of the different types of AOCs currently available,focusing on their clinical development for human use.展开更多
One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) ...One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.展开更多
Stroma--free hemoglobin (SFHb) was prepared from fresh or out--dated whole blood by lysing red cells. At different temperatures, pyridoxal 5--phosphate (PLP) was added in a 4:1 molar-ratio to the Hb tetramer followed ...Stroma--free hemoglobin (SFHb) was prepared from fresh or out--dated whole blood by lysing red cells. At different temperatures, pyridoxal 5--phosphate (PLP) was added in a 4:1 molar-ratio to the Hb tetramer followed by reduction with NaBH4 under N2 for 16 hrs subsequenl crosslinking by glutaraldehyde in presence of lysine for 14--16 hrs. Yielded soluble pyridoxalated polyhemoglobin (Poly Hb--P). 5%--20% gradient SDS--PAGE showed the change of the Hb molecular weight (MW) after crosslinking. Gel chromatography showed that the poly Hb--P had a continuous distribution of molecular weight with the range from about 65,000 to 600,000 Dalton. The poly Hb--P solution provided a normal oxygen carrying with 23.1 of P50, at pH 7.24 or 26.1 of P50 at pH 7.24展开更多
Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that inc...Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that include infection,short shelf life,and blood type mismatching.Artificial oxygen carriers produced using hemoglobin(Hb)are designated as Hb-based oxygen carriers(HBOCs),which are anticipated for use as biomaterials that have potential to resolve issues of transfusion by a radical paradigm shift.Various HBOCs,nanometer-sized to micrometer-sized bioparticles having an oxygen-carrying function,are developed for use as substitutes for red blood cells(RBCs).This paper presents an overview of the classification of HBOCs with reference to their histories,preparations,structures,functions,and in vitro and in vivo properties.Additionally,we give a more detailed introduction of our academic studies of liposome encapsulated Hb,designated as Hb-vesicles(HbV),which mimic the physiologically important corpuscular structure of RBCs.This review outlines perennial efforts and approaches to mimic RBC functions through chemical,genetic,and encapsulation techniques.It will provide important insights into the eventual realization of an alternative for RBC transfusion.展开更多
Oxygen is essential for sustaining life,maintaining physiological homeostasis,and supporting a wide range of therapeutic applications.Hemoglobin-based oxygen carriers(HBOCs)have long been explored as potential substit...Oxygen is essential for sustaining life,maintaining physiological homeostasis,and supporting a wide range of therapeutic applications.Hemoglobin-based oxygen carriers(HBOCs)have long been explored as potential substitutes for red blood cells(RBCs)due to their inherent oxygen transport capability.However,their clinical translation has been constrained by issues such as vasoactivity,oxidative stress-induced toxicity,and short circulation half-life.Recent advances in functional polymer science have provided new opportunities to overcome these barriers,with strategies including hemoglobin-polymer conjugation and encapsulation enabling the development of HBOCs with improved safety and efficacy.This review summarizes recent progress in the use of functional polymers for HBOC development,outlines key methods for performance evaluation,and discusses their current status and future prospects in diverse biomedical contexts,including blood substitution,ischemia-reperfusion injury and ischemic stroke therapy,tissue engineering,and cancer treatment.展开更多
文摘The demand for homologous blood transfusions has reached an unprecedented level,driven by a declining donor population and the ever-increasing need for blood products.While significant advancements have been made in medical equipment and techniques,a critical gap remains in developing an effective alternative to conventional blood transfusion.Medical research to find a proper blood substitute involves many previous experiments.The search for a blood substitute has been ongoing for patients for whom human blood is unavailable,with a few products showing promise in this field.Recent advancements in medical innovation have begun to address this challenge,notably through the development of artificial oxygen carriers(AOCs).These laboratory-synthesized alternatives to traditional blood transfusions offer a means of bypassing the need for human blood,particularly packed red blood cell(pRBC)transfusions.While AOCs fulfill the singular,critical role of in vivo oxygen delivery,the term is frequently used interchangeably with the broader concept of artificial blood.Various AOC products are currently in different stages of clinical development.Most Notable examples include Perftoran,which has been approved in Russia,Kazakhstan,Ukraine,the Kyrgyz Republic,and Mexico and has been administered to over 35,000 patients.Another significant product,Hemopure,has received clinical use approval in South Africa and Russia and has obtained expanded use approval from the United States Food and Drug Administration(USFDA).This article examines the landscape of AOCs,including their preparation methods,available products,regulatory approval status,current applications,limitations,and potential for future use in medical practice.This review article offers an overview of the different types of AOCs currently available,focusing on their clinical development for human use.
基金supported by the Biomedical EPR Facility of the University of Essexgranted by the EPSRC funded UK National Service for Computational Chemistry Software(NSCCS,1996-2017)Imperial College London。
文摘One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.
文摘Stroma--free hemoglobin (SFHb) was prepared from fresh or out--dated whole blood by lysing red cells. At different temperatures, pyridoxal 5--phosphate (PLP) was added in a 4:1 molar-ratio to the Hb tetramer followed by reduction with NaBH4 under N2 for 16 hrs subsequenl crosslinking by glutaraldehyde in presence of lysine for 14--16 hrs. Yielded soluble pyridoxalated polyhemoglobin (Poly Hb--P). 5%--20% gradient SDS--PAGE showed the change of the Hb molecular weight (MW) after crosslinking. Gel chromatography showed that the poly Hb--P had a continuous distribution of molecular weight with the range from about 65,000 to 600,000 Dalton. The poly Hb--P solution provided a normal oxygen carrying with 23.1 of P50, at pH 7.24 or 26.1 of P50 at pH 7.24
基金supporting to our research group with grants from the Japan Society for the Promotion of Science (JSPS)the Japan Agency for Medical Research and Development(AMED).
文摘Blood transfusions are regarded as the most well-known and frequently performed cell transplantations.Although current transfusion systems are sophisticated,they cannot be freed from the inherent difficulties that include infection,short shelf life,and blood type mismatching.Artificial oxygen carriers produced using hemoglobin(Hb)are designated as Hb-based oxygen carriers(HBOCs),which are anticipated for use as biomaterials that have potential to resolve issues of transfusion by a radical paradigm shift.Various HBOCs,nanometer-sized to micrometer-sized bioparticles having an oxygen-carrying function,are developed for use as substitutes for red blood cells(RBCs).This paper presents an overview of the classification of HBOCs with reference to their histories,preparations,structures,functions,and in vitro and in vivo properties.Additionally,we give a more detailed introduction of our academic studies of liposome encapsulated Hb,designated as Hb-vesicles(HbV),which mimic the physiologically important corpuscular structure of RBCs.This review outlines perennial efforts and approaches to mimic RBC functions through chemical,genetic,and encapsulation techniques.It will provide important insights into the eventual realization of an alternative for RBC transfusion.
基金financially supported by the Major Scientific and Technological Infrastructure Cultivation Projects of Jiangsu Province,Chinathe National Natural Science Foundation of China(Grant No.32301189)+1 种基金the Natural Science Foundation of Jiangsu Province(Grant Nos.BK20220824,BK20222002)the Jiangsu Funding Program for Excellent Postdoctoral Talent(Grant No.2025ZB578)。
文摘Oxygen is essential for sustaining life,maintaining physiological homeostasis,and supporting a wide range of therapeutic applications.Hemoglobin-based oxygen carriers(HBOCs)have long been explored as potential substitutes for red blood cells(RBCs)due to their inherent oxygen transport capability.However,their clinical translation has been constrained by issues such as vasoactivity,oxidative stress-induced toxicity,and short circulation half-life.Recent advances in functional polymer science have provided new opportunities to overcome these barriers,with strategies including hemoglobin-polymer conjugation and encapsulation enabling the development of HBOCs with improved safety and efficacy.This review summarizes recent progress in the use of functional polymers for HBOC development,outlines key methods for performance evaluation,and discusses their current status and future prospects in diverse biomedical contexts,including blood substitution,ischemia-reperfusion injury and ischemic stroke therapy,tissue engineering,and cancer treatment.
